Three independent studies from our research group have now demonstrated large and reliable relationships between psychological stress and wound healing. We showed that a chronic stressor, caring for a patient with Alzheimer's disease effected healing of a dermal wound. We have also shown that an acute and more enduring stressor significantly affected the speed of closure of an oral wound. Recent results obtained using a mouse model were comparable to the studies with human subjects. The immune system lays a major role in the regulation of wound repair and stress can alter the cellular immune response including the production of pro-inflammatory cytokines, which are important for wound healing. We believe that links between distress and immunity have important health consequences for older adults since immune function declines with aging. If psychological stress can slow the healing of a small wound, then healing of larger wounds, and minor and major surgeries, could be affected by stress. In this Program Project Grant, we propose four different projects to explore these very important relationships. Project 1 will determine if a model for short term stress can impact on the secretion of pro-inflammatory cytokines, stress hormones, and wound healing. Project 2 will determine if personality trait/slate put individuals at risk for adverse outcomes in wound healing and if aging exacerbates these interactions. Project 3 will use a mouse model to study the mechanisms underlying age and stress related changes in neuroendocrine factors, chemokines, and inflammatory cytokines which are responsible for altered wound healing observed in stressed mice. Project 4 will focus on the mechanisms underlying the effects of stress and aging on spinal cord injury using a mouse model. There are also four cores; Core A the administrative core; Core B the statistical analysis and data management core; Core C the immunohistopathology core, and Core D the endocrinology core. The research on the relationship among the central nervous system, the immune and endocrine systems and stress in older individuals may contribute to the understanding of how stress can affect wound healing.